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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nosaka, Shuichi Matsuura, Hiroshi Kojima, Akiko Omatsu-kanbe, Mariko Kitagawa, Hirotoshi |
| Description | Author Affiliation: Kojima A ( Department of Anesthesiology, Shiga University of Medical Science, Otsu, Shiga, Japan. akiko77@belle.shiga-med.ac.jp) |
| Abstract | BACKGROUND AND PURPOSE: The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH: Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (I(f) ), T-type and L-type Ca²â º currents (I(Ca,T) and I(Ca,L) , respectively), and slowly activating delayed rectifier Kâ º current (I(Ks) ), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS: In isolated SA node cells, sevoflurane (0.12-0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased I(f) , I(Ca,T) , I(Ca,L) and I(Ks) by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS: Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on I(f) , I(Ca,T) and I(Ca,L) . These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 166 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2012-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Anesthetics, Inhalation Pharmacology Methyl Ethers Sinoatrial Node Physiology Action Potentials Drug Effects Animals Cells, Cultured Guinea Pigs Heart Rate Cytology Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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